The US Food and Drug Administration and Japan’s Takeda Pharmaceutical Co have informed doctors of an increased risk of fractures in women associated with the firm’s diabetes drug Actos.
The warning comes after an analysis of the drugmaker's clinical trial database for Actos (pioglitazone) which showed more reports of fractures in female patients taking the treatment than those taking a comparator (either placebo or active).
The analysis included more than 8,100 patients taking Actos, and over 7,400 patients taking a placebo or alternative drug, the FDA said, noting that the majority of fractures were in the forearm, hand and wrist, foot, ankle, fibula and tibia. The patients were followed for up to three-and-a-half years and Takeda noted that the observed excess risk of fractures for women in this data set on pioglitazone is 0.8 fractures per 100 patient years of use.
In a letter to physicians, Dr Robert Spanheimer of Takeda wrote that the reason for the finding was unknown, but noted that "none of the pioglitazone studies in the database addressed, or were designed to study, the effect on bone, but fractures were collected as adverse events." Because of the limitations of the data available, he said multiple risk factors for fractures cannot be excluded as confounding variables but "further evaluation of these findings is ongoing," adding that there was no increased risk of fracture identified in men.
Takeda and the FDA said the risk of fracture should be considered before initiating pioglitazone therapy in women with type 2 diabetes and the company is working with the agency to sort out the correct wording to the label regarding the aforementioned risk.
The news comes less than a month after GlaxoSmithKline alerted doctors that long-term use of its diabetes drug Avandia (rosiglitazone), another thiazolidinedione like Actos, has been linked to an increased incidence of fractures in women. GSK informed the FDA of its findings after a safety review of the data from a large-scale clinical study of over 4,000 patients with type 2 diabetes.
Actos sales in the USA for the nine months ended December 31, 2006, reached 209 billion yen (about $1.77 billion), while Avandia brought in £324 million into GSK’s coffers in the fourth quarter but the drugs are now facing competition from a newer class of diabetes products, the dipeptidyl peptidase-4 inhibitors, headed by Merck & Co’s Januvia (sitagliptin).